Adenoviral vectors, including replication-defective adenoviral vectors, are being used as gene delivery vehicles for a wide range of transgenes in pre-clinical and clinical studies across many pathological indications. Intravenous administration of recombinant adenoviral vectors results in the transduction of hepatocytes, expression of the encoded transgenes and detectable circulating levels of secreted transgene products.
Delivery of low amounts of recombinant adenoviral particles can lead to low or undetectable levels of an encoded transgene product. Delivery of large amounts of adenoviral particles containing a therapeutic nucleic acid can result in high levels of the expressed transgene. High expression levels of adenovirus particles containing a therapeutic transgene can lead to complications such as liver toxicity. Therefore, there is a need in the art for better control of transgene expression in subjects treated with recombinant viral vectors.